Survivors of Hodgkin lymphoma treated as adolescents or adults are at increased risk of cardiovascular diseases throughout their lives, according to results of a retrospective cohort study of 2,524 Dutch patients followed for a median of 20 years. “Treating physicians and patients should be aware of the persistently increased risk of cardiovascular diseases throughout life, and the results of our study may direct guidelines for follow-up of patients with Hodgkin lymphoma,” Frederika A. van ­Nimwegen, MSc, of the Netherlands Cancer Institute, Amsterdam, advised in JAMA Internal Medicine.

All patients were diagnosed with Hodgkin lymphoma when younger than 52 years (median age, 27.3 years), had been treated from 1965 through 1995, and had survived for 5 years since their diagnosis. Among the 2,524 patients, 2,052 individuals (81.3%) had received mediastinal radiation, and 773 patients (30.6%) had received anthracycline-containing chemotherapy.

At a median follow-up of 20.3 years (range, 5–47 years), the researchers identified 1,713 cardiovascular events in 797 patients, with 410 patients having two or more events. The most frequently occurring cardiovascular disease was coronary heart disease, with 401 patients developing it as their first event, followed by valvular heart disease (374 events) and heart failure (140 events). The median intervals between Hodgkin lymphoma treatment and first cardiovascular disease events were 18 years for coronary heart disease, 24 years for valvular heart disease, and 19 years for heart failure.

Cumulative Risks

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after diagnosis, and 51% of patients with a cardiovascular disease had multiple events. For patients treated before age 25, the cumulative risk at 60 years of age or older was 20% for coronary heart disease, 31% for valvular heart disease, and 11% for heart failure as first events.

“Compared with the general population, four- to sevenfold increased risks of coronary heart disease or heart failure are observed 35 years or more after Hodgkin lymphoma treatment, resulting in 857 excess cardiovascular events per 10,000 person-years,” the researchers reported. Although patients treated before 25 years of age had the highest relative risks, “substantial absolute excess risks were also observed for patients treated at older ages,” the authors added.

“Adjusted for year of Hodgkin lymphoma diagnosis, sex, and ever smoking, mediastinal radiotherapy and anthracycline-containing chemotherapy were associated with an increased risk of any cardiovascular disease,” the investigators noted. Mediastinal radiotherapy increased the risk of coronary heart disease, valvular heart disease, and heart failure, whereas anthracycline-containing chemotherapy increased the risks of valvular heart disease and heart failure as first events compared with patients who did not receive those cancer treatments. “Radiation below the diaphragm or vincristine-containing chemotherapy did not influence the risks of any cardiovascular disease,” the researchers stated.

“No interactions on a multiplicative scale were found between mediastinal radiotherapy and anthracycline dose or mediastinal radiotherapy and smoking; the joint effects of these outcomes appeared to be additive rather than multiplicative,” the authors wrote.

Accompanying Commentary

“This work by van Nimwegen et al can specifically help physicians identify their highest-risk patients: those with a history of Hodgkin lymphoma who were treated at a younger age and those who are the longest from treatment,” Emily Tonorezos, MD, MPH, of the Weill Cornell Medical College, New York, and Linda Overholser, MD, of the University of Colorado Denver School of Medicine, Aurora, wrote in a related commentary.

“For most encounters, starting by asking a few key cancer history questions will help identify these patients: (1) What kind of cancer did you have? (2) How old were you when your lymphoma was diagnosed? (3) Did you receive chest radiotherapy? (4) Did you receive doxorubicin (many patients know it by the brand name Adriamycin [the red medicine])? Our clinical experience has been that patients typically know the answers to these basic questions, and these responses will go a long way toward identifying at-risk patients. Nonetheless, the future of good care for cancer survivors will require establishment of the evidence-based best practices for this population,” the commentary concluded. ■